The purpose of this project is to utilize genomic data from many related organisms in order to learn more about functions of eukaryotic DNA, both coding noncoding. For coding sequences, we discovered that amino-acid composition of proteins of modern organisms is still far from equilibrium, despite over 3 billion years of evolution. Also, we ascertained the complete distribution of coefficients of selection against amino-acid replacements in human proteins. For non-coding transcribed sequences, we developed a method for identification of regions in multiple sequence alignments thermodynamically suitable for targeting by consensus oligonucleotides. We also studied the mammalian transcriptome and the function of non-coding DNA sequences. For untranscribed sequences, we investigated contexts of 5'-enhancers which are associated with tissue-specific expression of the corresponding genes.